Sulfur compounds as inhibitors of enzymatic activity of a snake venom phospholipase A2: benzyl 4-nitrobenzenecarbodithioate as a case of study

ABSTRACT: Snakebite is a neglected disease with a high impact in tropical and subtropical countries. Therapy based on antivenom has limited efficacy in local tissue damage caused by venoms. Phospholipases A2 (PLA2) are enzymes that abundantly occur in snake venoms and induce several systemic and local effects. Furthermore, sulfur compounds such as thioesters have an inhibitory capacity against a snake venom PLA2. Hence, the objective of this work was to obtain a carbodithioate from a thioester with known activity against PLA2 and test its ability to inhibit the same enzyme. Benzyl 4-nitrobenzenecarbodithioate (I) was synthesized, purified, and characterized using as precursor 4-nitrothiobenzoic acid S-benzyl ester (II). Compound I showed inhibition of the enzymatic activity a PLA2 isolated from the venom of the Colombian rattlesnake Crotalus durissus cumanensis with an IC50 of 55.58 μM. This result is comparable with the reported inhibition obtained for II. Computational calculations were performed to support the study, and molecular docking results suggested that compounds I and II interact with the active site residues of the enzyme, impeding the normal catalysis cycle and attachment of the substrate to the active site of the PLA2.

• Autores: Henao Castañeda, Isabel Cristina; Pereañez Jiménez, Jaime Andrés; Preciado Rojo, Lina María; Jios, Jorge L.
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2020
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/39536
• Acceso en línea: https://hdl.handle.net/10495/39536
• Palabra clave: Venenos de Crotálidos - química; Crotalid Venoms - chemistry; Crotalus; Simulación del Acoplamiento Molecular; Molecular Docking Simulation; Inhibidores de Fosfolipasa A2 - química; Phospholipase A2 Inhibitors - chemistry; Fosfolipasas A2 - química; Phospholipases A2 - chemistry; Proteínas de Reptiles - antagonistas & inhibidores; Reptilian Proteins - antagonists & inhibitors; Proteínas de Reptiles - química; Reptilian Proteins - chemistry; Compuestos de Azufre - química; Sulfur Compounds - chemistry; https://id.nlm.nih.gov/mesh/D003435; https://id.nlm.nih.gov/mesh/D017839; https://id.nlm.nih.gov/mesh/D062105; https://id.nlm.nih.gov/mesh/D064801; https://id.nlm.nih.gov/mesh/D054467; https://id.nlm.nih.gov/mesh/D030162; https://id.nlm.nih.gov/mesh/D013457
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/